Antifungal therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis

 

Abstract

Background

Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to colonisation of the lungs with the fungus Aspergillus fumigatus and affects around 10% of people with cystic fibrosis. ABPA is associated with an accelerated decline in lung function. High doses of corticosteroids are the main treatment for ABPA; although the long-term benefits are not clear, their many side effects are well-documented. A group of compounds, the azoles, have activity against Aspergillus fumigatus and have been proposed as an alternative treatment for ABPA. Of this group, itraconazole is the most active. A separate antifungal compound, amphotericin B, has been employed in aerosolised form to treat invasive infection with Aspergillus fumigatus, and may have potential for the treatment of ABPA. Antifungal therapy for ABPA in cystic fibrosis needs to be evaluated.

Objectives

The review aimed to test the hypotheses that antifungal interventions for the treatment of ABPA in cystic fibrosis:
1. improve clinical status compared to placebo or standard therapy (no placebo);
2. do not have unacceptable adverse effects.

If benefit was demonstrated, we aimed to assess the optimal type, duration and dose of antifungal therapy.

Search methods

We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings.

In addition, pharmaceutical companies were approached.

Date of the most recent search of the Group's Trials Register: 26 November 2009.

Selection criteria

Published or unpublished randomised controlled trials, where antifungal treatments have been compared to either placebo or no treatment, or where different doses of the same treatment have been used in the treatment of ABPA in people with cystic fibrosis.

Data collection and analysis

Two trials were identified by the searches; one is currently awaiting classification and one was not judged eligible for inclusion in the review.

Main results

No completed randomised controlled trials were included.

Authors' conclusions

At present, there are no randomised controlled trials to evaluate the use of antifungal therapies for the treatment of ABPA in people with cystic fibrosis. Trials with clear outcome measures are needed to properly evaluate this potentially useful treatment for cystic fibrosis.

 

Plain language summary

Treatments to fight fungal infections which cause allergic bronchopulmonary aspergillosis in people with cystic fibrosis

Allergic bronchopulmonary aspergillosis (ABPA) is an allergic lung reaction to a type of fungus (usually Aspergillus fumigatus) in some people with cystic fibrosis. It causes cough and wheezing and sometimes fever. If left untreated it can lead to chronic lung damage. ABPA is usually treated with a high dose of corticosteroids (also known as steroids). However, it has not been proved that corticosteroids can prevent lung function deteriorating in the long term. Also, long-term use of these drugs is linked to some serious side effects. Treating the fungus which causes ABPA may be an alternative to using high doses of steroids to combat the allergic reaction. No trials were found which we could include in the review. There are trials in people without cystic fibrosis which have shown that if treatment is given to reduce the fungus, the steroid dose can be reduced with no adverse effects. However, in one CF centre researchers observed that when treated with an anti-fungal agent in addition to steroids, several people became unable to produce enough cortisol (a hormone) in their adrenal glands in response to stress. There is not enough evidence for us to recommend the use of antifungal drugs in people with CF and ABPA. There should be a trial of these drugs to assess their effects in the long and the short term.

 

摘要

背景

抗黴菌療法對於囊狀纖維化病人的過敏性支氣管與肺麴菌病的治療

過敏性支氣管與肺的麴菌病(簡稱ABPA)，是煙色麴菌吸到肺部時所產生的過敏反應，大約有百分之十的囊狀纖維化病人會有此症狀。ABPA會造成肺功能的急速下降。儘管長期的效益仍不明確，也可能發生許多副作用，但高劑量的腎上腺皮質激素仍是ABPA的主要療法。有群化合物─氮雜茂(azoles)有對抗煙色麴菌的活性，被提出作為ABPA的替代療法。其中又屬伊曲康唑(itraconazole)最為活躍。另外的一個抑制真菌化合物─兩性黴素B(amphotericin B)，已被以噴霧的型式，用來治療煙色麴菌的侵入性感染，也可能可以用來治療ABPA。抗黴菌療法對於囊狀纖維化病人的ABPA的治療，需要評估。

目標

這審查的目的，在於求證「抗黴菌療法可用來治療囊狀纖維化病人的ABPA」，這個假設是否成立：1.相較於安慰劑或是標準療法(不使用安慰劑)，改善醫療的狀況；2.不要有不可接受的不良反應產生。如果顯示確實有所助益，我們希望能評估出殺菌療法最適宜的類型、時間與劑量。

搜尋策略

我們搜尋了考科藍囊狀纖維化與遺傳疾病小組的試驗紀錄，其中參考內容包括了完整的電子資料庫以及人工整理的相關期刊與會議紀錄摘要。另外，也有與藥商接觸。 最近一次查尋該小組試驗紀錄的時間：2009年11月26日。

選擇標準

在公開或未公開的隨機臨床對照試驗中，用來治療囊狀纖維化病人的ABPA的抗黴菌療法與安慰劑或是不治療間的比較，或是相同療法不同劑量間的比較。

資料收集與分析

在搜尋中發現了兩個試驗；一個目前正待分類，而另一個被認為不適合這次審查的範疇。

主要結論

沒有完成的隨機臨床對照試驗可供參考。

作者結論

目前仍沒有隨機的臨床對照試驗，可用來評估用抗黴菌療法治療囊狀纖維化病人ABPA的效益。這項對於囊狀纖維化極有潛力的實用療法，需要有清楚結果的試驗來正式評估。

翻譯人

本摘要由臺灣大學附設醫院秦祥銘翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

治療囊狀纖維化病人ABPA的抗黴菌療法：過敏性支氣管與肺麴菌病(ABPA)是肺部對於一種真菌(通常是煙色麴菌)的過敏反應，會發生在一些囊狀纖維化病人的身上。它會導致咳嗽與喘息，有時會發燒。如果不治療會導致肺的慢性損害。ABPA同常以高劑量的腎上腺皮質素(也就是類固醇)來治療。然而就長期來看，腎上腺皮質素並未經證實得以防止肺功能的下降。同時，長時間使用這些藥物會導致一些嚴重的副作用。對抗引起ABPA的黴菌，可能是用高劑量類固醇抑制過敏反應外的另一項療法選擇。然而沒有試驗得以供這次審查參考。只有試驗是關於非囊狀纖維化的病人，記錄如果以此療法抗黴菌，那麼類固醇的用量也可降低，而不會有不良反應產生。然而，在某個囊狀纖維化中心，研究員觀察到：抗黴菌製劑與類固醇並用時，有些人在面對壓力時，腎上腺會變得無法產生足夠的皮質醇(一種荷爾蒙)。還沒有足夠的佐證讓我們得以推薦使用抗黴菌藥劑，來治療囊狀纖維化以及ABPA的病人。應該要做個試驗，來評估這些藥劑分別在短期以及長期的效力。